Solid pharmaceutical formulation comprises usually an active ingredient in admixture with pharmaceutically acceptable excipients, said excipients being used in order to improve the easiness of administration of the drug and also to improve the formability of the formulation (cf. JP-A-11-286456). Hitherto, there has been usually used starch as an excipient for solid pharmaceutical formulations. Starch has advantageously been used as an excipient for pharmaceutical formulation because of excellent stability and safety and further when it is used as a carrier for granules prepared by extrusion granulation technique, it improves plasticity of the granules owing to water-retentivity thereof, and thereby alleviates the burden onto the screen of extrusion granulator and gives easier procedure of the granulation step.
On the other hand, starch has physical properties that the particles thereof are hard and have round shape in dry state, and hence when usual starch is used as an excipient for solid pharmaceutical formulation, the formed solid formulation has inferior physical strength. The less strength of solid pharmaceutical formulation is likely to cause breakage failure of the solid formulation and hence cause of lower yield of the product and lower efficiency in packaging step thereof. Accordingly, it is required to improve the physical strength of the solid pharmaceutical formulation when usual starch is used as an excipient for solid pharmaceutical formulation.
Moreover, the solid pharmaceutical formulation prepared by using usual starch as an excipient is also insufficient in drug release properties when administered, and hence, it is also required to modify the formulation so that the drug is rapidly released in the digestive tract.
By the way, it is known that pre-gelatinized starch (α-starch) has properties to become pasty when mixed with water, and by utilizing the properties, the pre-gelatinized starch is usually added as a binder in a small amount for preparing a solid pharmaceutical formulation. The pre-gelatinized starch has superior digestibility within digestive tract in comparison with usual starch and is easily digested within digestive tract, and hence it is preferable for incorporating into solid pharmaceutical formulations.
However, when the pre-gelatinized starch is incorporated as an excipient in a large amount into the solid pharmaceutical formulation, the mixture becomes pasty when it is subjected to wet-granulation, which causes difficulty in the preparation of the pharmaceutical formulation. Further, even when the pasty mixture of the pre-gelatinized starch and an active medical component is dried, it becomes undesirably a hard aggregated product, which is difficult to pulverize for preparing pharmaceutical formulation.
It has never been known to prepare a solid pharmaceutical formulation by a hydrolytic granulation technique using a pre-gelatinized starch, and there has not yet been established a technique of preparing a pharmaceutical formulation containing a pre-gelatinized starch in a ratio of about 10% by weight or more and having the desired strength.